Fatal surfactant deficiency in two siblings caused by a novel ABCA3 ...

Hofmeister J, Bruder E, Aslanidis C, Hammer J,
Schmitz G, Bührer C, Department of Neonatology
(HJ, BC), University Children‘s Hospital of Basel,
Institute of Pathology (BE), University Hospital of
Basel, Institute for Clinical Chemistry (AC), Regensburg
University Medical Center, Department of Pediatric
Pneumonology (HJ), University Children‘s Hospital
of Basel
© Swiss Society of Neonatology, Thomas M Berger, Webmaster
Pulmonary surfactant lowers surface tension and pre-
vents atelectasis at end-expiration. It is composed of
phospholipids and proteins synthesized within type II
cells. The mixture is packaged into specialized orga-
nelles called lamellar bodies which are extruded into
the alveolar lumen by exocytosis.
A complex and tightly regulated cycle of synthesis,
processing, transport, secretion, degradation, re-up-
take or clearance and reprocessing involves both the
phospholipids and protein components of pulmonary
surfactant.
Defective synthesis of the essential surfactant compo-
nent surfactant protein-B, or impaired lamellar body
transport leads to fatal neonatal lung disease. At pre-
sent, mutations in genes, encoding surfactant prote-
in-B (SP-B) or ATP binding cassette transporter family
member ABCA , have been shown to underlie fatal
hereditary neonatal interstitial lung disease. While SP-B
is indispensable for surfactant function, the lipid transporter
ABCA targets surfactant phospholipids to the
lamellar bodies and is necessary for lamellar body biogenesis,
SP-B processing and lung development late
in gestation (1). Here, we present the clinical course of
two related infants who succumbed from severe hypoxemic
respiratory failure caused by a novel mutation in
the ABCA gene.
INTRODUCTION